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Ozone enhancement of platinum asthma in a primate model.

The effect of ozone (10028156) on platinum (7440064) induced pulmonary hypersensitivity was studied in monkeys. Adult cynomolgus monkeys were exposed by inhalation to 1 part per million (ppm) ozone, 200 micrograms/cubic meter (microg/m3) ammonium- hexachloroplatinate (16919587) (AHCP), or to 1ppm ozone plus 200microg/m3 AHCP 6 hours daily, 5 days per week for 12 weeks. The animals were observed for signs of intoxication. The animals underwent bronchoprovocation challenge with sodium- hexachloroplatinate (16923583) (SHCP) and methacholine (55925), SHCP threshold skin tests, and pulmonary function testing before and 2 weeks after exposure ended. Sera were collected and assayed for immunoglobulin-E, (IgE), immunoglobulin-G, and platinum specific IgE before and after exposure. The animals appeared to tolerate exposure with no overt ill effects being noted. Four of eight monkeys exposed to platinum plus AHCP developed postexposure positive skin sensitivity at a SHCP concentration of 10(-6) grams per milliliter. The immunologic parameters were not significantly affected by any of the exposure regimens. Pulmonary function was not significantly affected by any of the exposures. Exposure to AHCP or ozone alone had no significant effect on postexposure platinum or methacholine reactivity. Ozone plus AHCP significantly reduced the amount of SHCP and methacholine necessary to increase average pulmonary flow resistance. The authors conclude that combined inhalation exposure to 200microg/m3 AHCP and 1ppm ozone causes platinum and methacholine bronchial hyperreactivity. The findings support the usefulness of cynomolgus monkeys as models for studies of acquired pulmonary hyperreactivity, allergic sensitization, and asthma.